Neuromesoderm progenitors (NMPs) are a distinct stem cell population that express both the mesoderm marker brachyury (T) and the neural marker Sox2, and are required for axial growth in vertebrates. They are capable of binary fate choice, differentiating as either neural or mesodermal progenitors. Tbx6, a downstream target of T, has been proposed to act as a fate switch, stimulating the mesodermal differentiation of NMPs, but the timing of this fate commitment is unclear. On p. 4522, Ramkumar Sambasivan and co-workers report the identification of cells in the mouse primitive streak and later in the tail bud that co-express Tbx6 and Sox2. These Tbx6+/Sox2+ cells represent a novel transient subpopulation of NMPs primed for mesodermal differentiation. Tbx6-null NMPs in mouse embryos are incapable of mesodermal commitment and default to neuronal differentiation, which strikingly results in ectopic formation of neural tubes. The authors show that this phenotype is stronger in more posterior regions, suggesting a differential requirement for Tbx6 in trunk versus tail NMPs. These data confirm the proposed ‘fate switch’ role of Tbx6 in mesodermal commitment of NMPs, and further our understanding of NMP differentiation and their role in body axis elongation.